The World Health Organization estimates that tuberculosis (TB) elimination can be achieved by 2050 if 70% of estimated sputum smear-positive TB cases are identified and 85% are treated successfully.1-3 Unfortunately, smear-positive TB case detection rates are far below the 70% target in most high burden countries.1 To improve case detection and management, the Tuberculosis Coalition for Technical Assistance developed evidence-based guidelines called the International Standards for TB Care (ISTC).6 Adherence to ISTC-recommended practices for TB suspect evaluation is poor in low-income countries.5,7 Thus, improving ISTC implementation offers a tremendous opportunity to reduce the global burden of TB. Our long-term objective is to determine whether a multi-faceted intervention to improve ISTC implementation reduces TB-related morbidity and mortality in low-income countries. The proposed multi-faceted intervention addresses three categories of factors that are critical for changing behavior: (1) predisposing factors - knowledge or attitudes that either support or inhibit the desired behavior;(2) enabling factors - characteristics of an individual or environment that facilitate the desired behavior;and (3) reinforcing factors -anticipated consequences of following the desired behavior.9,10 Thus, the multi-faceted intervention includes (1) ISTC training modules to improve provider knowledge and attitudes toward ISTC;(2) single-specimen microcopy (a more efficient smear microscopy strategy) to enable ISTC adherence;and (3) a performance feedback system to reinforce ISTC adherence. The pilot studies proposed in this R21 application are designed to evaluate the feasibility and impact of each of these intervention components. The data will inform a future R01 application to assess whether a multi-faceted intervention to improve ISTC adherence actually increases TB case detection. For the pilot studies, our hypothesis is that each component will improve provider adherence to ISTC-recommended TB suspect evaluation practices. The pilot studies will take place within the Uganda Infectious Disease Surveillance Network (UIDSN), which collects data on TB care at 6 government health centers (>100,000 annual patient encounters) that are typical of those seen throughout sub-Saharan Africa. The research subjects are the approximately 50 providers (3- 4 clinicians, 1-2 laboratory technicians, and 2-3 nurses per health center) working at the 6 UIDSN health centers. To test our hypothesis, each intervention component will be introduced at the 6 UIDSN health centers in a sequential fashion. Data from approximately 2500 TB suspects will be used to objectively measure provider adherence to ISTC before and after introduction of each intervention component. If successful, the proposed studies could help reverse the current trend of rising global TB incidence and are consistent with NIAID's mission to prevent infectious diseases that threaten millions of lives. In addition, this research will lead to a better understanding of the factors and types of interventions associated with successful evidence-based guideline implementation and strengthened health systems in resource-limited settings. PUBLIC HEALTH RELEVANCE: The objective of this R21 application is to improve adherence to evidence-based guidelines for the evaluation of people suspected of having tuberculosis (TB), one of the most common infectious diseases and a leading cause of death worldwide. In the resource-limited settings in which TB is most common, better implementation of evidence-based guidelines could represent a cost-effective strategy to increase detection and treatment of the most infectious TB cases and help achieve the Millennium Development Goal of reversing the annual increase in global TB incidence.